Endoscopic resection with one port placement: a newly developed technique for the safe management of advanced endoscopic resection for gastric gastrointestinal stromal tumors

DOI: https://doi.org/10.21203/rs.3.rs-1560815/v1

Abstract

Backgrounds

: Endoscopic full-thickness resection (EFTR) without laparoscopic assistance—pure EFTR—is an emerging, less invasive treatment for gastrointestinal stromal tumors (GISTs). However, the technique has seldom been applied outside of China due to concerns about pneumoperitoneum, maintenance of endoscopic view, and endoscopic suturing regarding its procedure. This study aimed to evaluate the efficacy and safety of endoscopic resection with one port placement (EROPP) for gastric GISTs.

Methods

This retrospective study included 14 patients with gastric GISTs originating from the muscularis propria who underwent EROPP between 2019 and 2021. One camera port was inserted in the umbilicus before starting the endoscopic procedure to maintain intra-abdominal pressure, which was monitored and adjusted via this port. While allowing for conversion to laparoscopic surgery if needed, EFTR was performed as follows: (1) circumferential incision of the mucosal and submucosal layer around the lesion by typical endoscopic submucosal dissection; (2) an intentional perforation and subsequent seromuscular resection using dental floss and an endo-clip for traction; and (3) closure of the gastric full-thickness defect with an over-the-scope-clip (OTSC) after peroral retrieval of the specimen. We retrospectively assessed the short-term outcomes and safety.

Results

All procedures were completed successfully without conversion to laparoscopic surgery. The median size of resected tumors was 23 mm (range, 10–35 mm) and the median procedure time was 37 min (range, 22–95 min). The rates of en bloc and curative resection were 100% and 86%, respectively. In two cases, another port was added to aspirate leaking fluid or to check the condition of the endoscopic closure. All gastric defects were endoscopically closed, mainly using OTSCs. The recovery course for all patients was uneventful and no adverse events were reported

Conclusions

EROPP is a safe and minimally invasive treatment for gastric GISTs and seems to be suitable as a pure EFTR procedure.

Introduction

It is known that gastric gastrointestinal stromal tumors (GISTs) have some malignant potential. However, regional lymph node metastasis is unusual for GISTs. Hence, a complete surgical resection of the lesion is the standard treatment for localized gastric GISTs. Furthermore, in the case of localized gastric GISTs (< 5 cm in size), depending on location and growth pattern, less invasive laparoscopic surgery involving laparoscopic and endoscopic cooperative surgery (LECS) procedures has been performed with an emphasis on improving the postoperative quality of life[1].

Endoscopic submucosal dissection (ESD) is a developed technique in the field of endoscopic treatments for gastrointestinal neoplasms. Recently, many endoscopic procedures derived from ESD have been successfully performed to remove gastric GISTs. Several authors in China have described favorable treatment outcomes for gastric GISTs using endoscopic full-thickness resection (EFTR) without laparoscopic support, namely pure EFTR[2–4]. In contrast, few authors outside of China have reported on this procedure. We focused on a few barriers for the non-implementation of pure EFTR in clinical practice outside of China: (1) management of the pneumoperitoneum and maintaining gastric intraluminal pressure; (3) how to handle luminal collapse; and (3) absence of reliable endoscopic full-thickness suturing devices. Since these concerns are directly related to safety, the introduction of the procedure is difficult for endoscopists who have no experience with pure EFTR. To address these issues, we introduced endoscopic resection with one port placement (EROPP) which is a hybrid EFTR procedure that minimizes the intervention of laparoscopic procedures and is a newly developed technique for the safe management of advanced endoscopic resection for gastric GISTs in November 2019.

Materials And Methods

Enrolled patients and tumors

From August 2019 to December 2021, 14 patients with gastric GISTs that originated from the muscularis propria underwent EROPP at Yokohama City University Medical Center. Before the treatment, all patients underwent esophagogastroduodenoscopy (EGD), CT scan, and endoscopic ultrasound (EUS) for the determination of the size, the layer of origin, and growth pattern of tumors. We confirmed that all patients met the following criteria before treatment: i) histological diagnosis of GIST via EUS-guided fine-needle aspiration (EUS-FNA); ii) intraluminal tumors without a massive extraluminal component; iii) tumor size < 35 mm; iv) no tumor ulceration; and v) no regional lymph node enlargement or distant metastasis on CT. All patients provided written informed consent before enrolling into the study. The Institutional Review Board of Yokohama City University approved this study (Facility IRB certification number: F210900029). 

Procedures of EROPP

EFTR was performed in the operating room under general anesthesia with tracheal intubation by a skilled endoscopist (K.H.). A single-channel endoscope with water jet (GIF-Q260J; Olympus, Tokyo, Japan) or a 2-channel multi-bending endoscope (GIF-2TQ260 M; Olympus) was used with a high-frequency power supply unit (VIO 300 D; ERBE Elektromedizin, Tübingen, Germany) for electrocoagulation. The EFTR procedure was performed using a 1.5-mm Dual knife (KD650Q; Olympus Medical Systems, Tokyo, Japan). A 4-mm-long transparent hood was attached to the tip of an endoscope (D-201-11804 or D-201-13404; Olympus Medical Systems, Tokyo, Japan) to facilitate optimal field visualization. Carbon dioxide insufflation was used during all cases. Prior to performing the endoscopic procedure, a camera port was inserted by a certified laparoscopic surgeon in the umbilicus to avoid intra-abdominal compartment syndrome due to pneumoperitoneum. A laparoscope was used for exploration of intraabdominal adhesions. In addition, the liver, serosal surfaces, peritoneum, omentum, and mesentery were systematically inspected. Pneumoperitoneum was maintained at 10 mmHg during exploration. After the setup to convert to laparoscopic surgery immediately, EFTR procedure was performed as follows (Fig 1 and Video 1): (i) a saline or 10% glycerin solution mixed with sodium hyaluronate (MucoUp; Johnson & Johnson Medical Company, Tokyo, Japan) was injected into the submucosal layer after marking just around the lesion; (ii) circumferential incision of the mucosal and submucosal layer around the lesion by typical ESD technique was performed; (iii) intentional perforation and subsequent seromuscular resection using dental floss and an endo-clip as a traction method were completed; and (iv) the gastric full-thickness defect was closed using an over-the-scope-clip (OTSC, Ovesco Endoscopy, Tübingen, Germany) after peroral retrieval of the specimen. Additional OSTCs or endo-clips were used to achieve a complete closure if the defect did not close completely using a single OTSC. After endoscopic closure, laparoscopic checks for air leaks were performed, taking advantage of the fact that the intra-abdominal pressure does not change even if the gastric lumen is inflated. A gastrointestinal decompression drainage tube was routinely inserted in all cases after completion of the procedure.

Postoperative management

Postoperative treatment included gastrointestinal decompression, proton pump inhibitor (PPI) therapy, and antibiotics. The gastrointestinal decompression drainage tube was withdrawn within 24 to 48 hours. Patients were kept on nothing per os for at least 48 hours and second-look endoscopy was routinely performed on postoperative (POD) 3 to check the condition of the endoscopic closure. Patients were then moved to liquid meals on POD4, and they gradually returned to a normal diet on POD8. All patients received a standard intravenous dose of PPI for 4 days and were switched to oral PPI for 4 weeks after EROPP. Antibiotics were prescribed for 3 days to prevent postoperative infection.

Definition

En bloc resection was defined as resection of the lesion in a single piece with no endoscopically visible residual tumor. R0 resection was defined as an en bloc resection wherein the lateral and vertical margins of the specimens were free of tumor cells. The procedure time was measured from the start of the submucosal injection to the removal of the lesion.

Statistical analysis

Simple descriptive statistics were used to report proportions and characteristics of the study using Microsoft Excel. Data are presented as mean, median, and range.

Results

Clinicopathological characteristics and treatment outcomes are summarized in Table 1. All EROPP procedures were completed successfully without conversion to laparoscopic surgery. In two cases, an additional port was required to aspirate the leaked liquid or to retract the liver to check the condition of the endoscopic closure via the laparoscopic view. The median size of the resected tumors was 23 mm (range, 10–35 mm). The median procedure time was 37 min (range, 22–95 min). All tumors were removed en bloc endoscopically, and the gastric wall defects were successfully closed with OTSCs without the requirement for laparoscopic closure. No patient had an OTSC detachment on second-look endoscopy. The R0 resection rate was 86%: R0 classification could not be applied in the remaining two cases, because the histological margin was unclear due to cauterization in a tiny area. The final histological diagnosis was GIST in all cases. All patients followed an uneventful course without any postoperative adverse events. During the median follow-up period of 14 months (range, 2–29 months), there was no evidence of recurrence in any patient.

Table 1

Clinicopathological characteristics and treatment outcomes for each patient

Case

Gender

Age

Location 1

Location 2

Tumor size (mm)

Procedure time (min)

R0 resection

Histological tumor injury

Hospitalization

(days)

Risk classification*

Access ports

1

F

77

Body

GC

15

22

Yes

Absent

8

very low

1

2

M

76

Fundus

GC

24

38

Yes

Absent

9

low

1

3

F

67

Body

PW

13

20

Yes

Absent

8

very low

1

4

F

42

Body

LC

18

23

Yes

Absent

8

very low

1

5

F

57

Antrum

LC

10

40

Yes

Absent

9

very low

1

6

M

69

Fundus

GC

15

30

Yes

Absent

8

very low

1

7

M

85

Body

AW

30

49

Yes

Absent

9

low

1

8

F

80

Fundus

GC

35

40

Yes

Absent

9

low

2

9

M

73

Fundus

AW

30

35

No

Present

9

low

1

10

F

69

Fundus

GC

25

30

Yes

Absent

9

low

1

11

M

73

Cardia

PW

28

56

Yes

Absent

9

moderate

1

12

F

66

Body

LC

25

23

Yes

Absent

8

low

1

13

F

63

Body

LC

30

95

No

Present

9

low

2

14

M

73

Body

LC

22

30

Yes

Absent

8

low

1

GC, greater curvature LC, lesser curvature PW, posterior wall AW, anterior wall

*Modified Fletcher Classification.

   

Discussion

Herein, we reported a hybrid EFTR with minimal surgical intervention—EROPP—for gastric GISTs. EROPP has an important advantage of being able to keep the intra-abdominal pressure constant. This eliminates concerns about intra-abdominal compartment syndrome originating from the pneumoperitoneum and contributes to maintain the good visual endoscopic field. Consequently, we were able to obtain good treatment outcome for gastric GISTs despite a lack of experience with pure EFTR.

EFTR has been introduced as a treatment option for gastric GISTs (< 4 cm) originating from the muscularis propria, according to the American Society for Gastrointestinal Endoscopy (ASGE) guidelines.[5] However, pure EFTR has not been widely adopted in clinical practice. One of the barriers of pure EFTR is the management of pneumoperitoneum and how to prevent collapse in the gastric lumen. Pure EFTR procedures can potentially cause dangerously high pneumoperitoneum. Additionally, the intentional perforation of the gastric wall leads to an unclear visual field because intragastric gases could escape into the peritoneal cavity [6]. To overcome this, we tend to insufflate the lumen continuously to maintain a good visual field. This may cause excessive pneumoperitoneum, which gives rise to abdominal compartment syndrome. Although previous studies revealed that needle decompression can decompress the abdominal cavity, this can prevent the provision of a good endoscopic visual field after luminal collapses by intentional perforation[3, 6, 7]. In an experiment performed in pigs, Kamba et al. reported that the intra-abdominal pressure and the intragastric luminal pressure during EFTR were in equilibrium[8]. From this, it is considered that when the abdominal cavity is collapsed with a puncture needle, the gastric luminal pressure is also significantly reduced, which hinders the securing of the endoscopic visual field. Especially for endoscopists who have no experience with EFTR, collapse of the gastric lumen is a technical obstacle. In this case series, however, the intra-abdominal pressure was monitored and adjusted via a port during the procedure, thus enabling the procedure without any concern of excessive pneumoperitoneum. Additionally, maintaining a constant intra-abdominal pressure from the port also maintains the intra-gastric luminal pressure, which leads to a good endoscopic field of view during the procedure. For this reasons, en bloc resection could be achieved in all cases and R0 resection in most cases, which also resulted in a relatively short procedural time.

Another barrier for using pure EFTR is the absence of reliable endoscopic full-thickness suturing devices. Various methods and devices are available for gastric wall closure[9, 10]. A recent report suggested that OTSCs can be used to perform EFTR with defect closure for gastric tumors in the muscularis propria (tumor diameter < 2 cm)[11]. Similarly, this case series demonstrated that gastric full-thickness defects were successfully closed with OTSCs in all 14 cases. As shown in our video, the OTSC closure system enables us to achieve inverted seromuscular apposition[12, 13]. A previous study indicated that inverted serosal apposition provides a more durable and reliable repair than everted mucosal apposition[14]. In this procedure, defect closure using OTSCs is more reliable than purse-string suturing using an endoloop and endo-clips. In addition, when large defects led to incomplete closures, additional OTSCs or endo-clips were used to close the remaining portions, resulting in robust closure. Therefore, OTSC may be a reliable endoscopic full-thickness suturing device, given the uneventful postoperative course in this case series. When tumors are positioned on the gastric posterior wall, or the lesser or greater curvature sides, which are covered with fat tissue, the EFTR site may not be visible using one-port laparoscopic observation. However, even in such situations, a leak test can be performed by inflating the gastric lumen and confirming that the intra-abdominal pressure does not increase. Of course, where we can see the EFTR site with a laparoscopic camera, we can directly observe that the EFTR site is inverted and robustly closed. In this case series, all the gastric wall defects were successfully closed with OTSCs without requiring laparoscopic closure. This could be explained by the fact that the control and monitoring of intra-abdominal pressure via a port contribute to maintaining a good endoscopic field of view during the closure procedure. In addition, as shown on the video, when the liver interfered the laparoscopic view, we could immediately check the condition of the endoscopic closure via the laparoscopic view by retracting the liver through an additional port. Furthermore, if the defects were technically difficult to close in EROPP, we could immediately convert it to a laparoscopic hand-sewn closure using additional port access.

The LECS technique was developed in Japan as a gastric wedge resection procedure with minimal transformation of the stomach[15]. Since its inception, LECS-related procedures have developed rapidly, spreading not only in Japan but also worldwide[1]. According to the ASGE guideline, LECS was described as a hybrid EFTR, which is combined endoscopic and laparoscopic technique [5],[16]. On the other hand, most studies of pure EFTR for gastric GISTs have been performed in China[24]. A previous review article of pure EFTR reported that conversion to surgery due to either EFTR failure or adverse events was needed in only 0.8% of the procedures[17]. However, this procedure, which is dominated by experience from China, is still controversial in its global spread. Our EROPP, hybrid EFTR with minimal laparoscopic intervention, is excellent not only in terms of safety but also in the introduction of EFTR procedures and has the potential to be globally accepted. Our EROPP procedure is minimally invasive, compare to conventional hybrid EFTR as it requires less gastric wall resection and no omental resection, thereby preserving normal gastric emptying. In addition, our procedure is better than conventional hybrid EFTR in terms of cosmetic outcomes because most of the EROPP procedures were performed with only one port access in this case series. Although the indication for our EROPP is similar to that for conventional hybrid EFTR, the size of GISTs was no more than 35 mm in diameter in this case series, which is smaller than the indication for conventional hybrid EFTR since it is challenging to remove tumors > 35 mm diameter through the oral cavity. In terms of damage to the abdominal wall, pure EFTR is a less invasive treatment compared with our EROPP. However, as previously stated, many concerns about pure EFTR have not been addressed yet with currently available methods and devices. Because the efficacy and safety of pure EFTR remain poorly understood in the countries where pure EFTR has not been popularized, we should consider safety as a top priority. Our case series suggest that port assistance plays an important role to address many concerns about pure EFTR. Furthermore, with the experience of EROPP, we believe that inexperienced endoscopists were the catalyst for the introduction of EFTR and more endoscopists could learn the pure EFTR technique safely.

There are certain limitations in our study. First, this is a retrospective, single-center study. Second, the number of patients was small, requiring validation of our results in larger sample sizes. Moreover, endoscopic procedures in this case series were performed by an experienced endoscopist at a high-volume center.

To conclude, EROPP may be a safe, less invasive hybrid EFTR for gastric GISTs. The experience of EROPP may make pure EFTR more accessible to endoscopists with limited or no experience in pure EFTR.

Abbreviations

EFTR

endoscopic full-thickness resection

EROPP

endoscopic resection with one port placement

ESD

endoscopic submucosal dissection

EUS

endoscopic ultrasonography

EUS-FNA

endoscopic ultrasound-guided fine needle aspiration

GIST

gastrointestinal stromal tumor

LECS

laparoscopic and endoscopic cooperative surgery

MP

musucularis propria

OTSC

over-the-scope-clip

Declarations

Ethics approval and consent to participate

This study was approved by the Ethics Committee of Yokohama City University (approval number. F210900029), and the study was conducted following the provisions of the Declaration of Helsinki. All the patients had given their written informed consent for the procedure and the use of their data.

Consent for publication

Participants gave their consent for publication.

Availability of data and materials

All patient data and clinical images adopted are contained in the medical files of Yokohama City University Medical Center. The data supporting the conclusions of this article are included within the article and its figures.

Competing interests

The authors declare that they have no competing interests.

Funding

The work described herein was supported by departmental resources only.

Authors' contributions

Conception and design (KH, AS); acquisition of data (KH, AS, CS); analysis and interpretation of data (KH, AS, SM); drafting of the article (KH); critical revision of the article (KH, SM); statistical analysis (KH, AS); final approval of the article (KH, AS, CS, SS,TS,KS,CK,SM). All authors listed have contributed substantially to the design, data collection and analysis, and editing of the manuscript.

Acknowledgments

We thank Nobutsugu Abe for helpful advice on the idea and naming of EROPP.

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